How is zidovudine-induced anemia managed?

Management of Zidovudine-Induced Anemia

Zidovudine-induced anemia should be managed by dose interruption of zidovudine, consideration of erythropoietin therapy for moderate cases, and blood transfusions for severe cases with hemoglobin below 7.5 g/dL. 1, 2

Pathophysiology and Risk Factors

• Zidovudine (AZT) causes anemia through bone marrow suppression and should be used with caution in patients with pre-existing bone marrow compromise (granulocyte count <1,000/mm³ or hemoglobin <9.5 g/dL) 1
• Anemia typically develops early, within 2-4 weeks of starting zidovudine therapy 1
• Risk factors for developing zidovudine-induced anemia include:
  • Low baseline hemoglobin (<10.5 g/dL) 3
  • Advanced HIV disease 4
  • Concurrent use of other myelosuppressive medications 4
  • Older age 5
  • Pre-existing hematologic disorders such as thalassemia 6
  • Duration of prior antiretroviral therapy less than one year 5

Monitoring Recommendations

• Baseline hemoglobin levels should be >12 g/dL for females and >13 g/dL for males before initiating zidovudine therapy 4
• Frequent blood counts are strongly recommended to detect severe anemia, particularly in patients with advanced HIV disease 1
• Monitor hemoglobin every 2 weeks while on zidovudine therapy, especially during the first 8 weeks 1
• For patients with risk factors, more intensive monitoring may be required 3

Management Algorithm

Step 1: Assess Severity of Anemia

• Mild anemia (Hgb 10-12 g/dL): Consider close monitoring without intervention 4
• Moderate anemia (Hgb 7.5-10 g/dL): Consider dose interruption and/or erythropoietin 1
• Severe anemia (Hgb <7.5 g/dL): Requires dose interruption and possible transfusion 4

Step 2: Management Based on Severity

For Moderate Anemia (Hgb 7.5-10 g/dL):

• Interrupt zidovudine therapy until evidence of marrow recovery is observed 1
• Consider erythropoietin therapy if endogenous erythropoietin levels are ≤500 IU/L 2, 7
• Recommended erythropoietin dosing: 100-200 U/kg three times weekly 7
• Monitor response to erythropoietin therapy with weekly hemoglobin measurements 2

For Severe Anemia (Hgb <7.5 g/dL):

• Immediately interrupt zidovudine therapy 1
• Administer packed red cell transfusions (2-3 units) 4
• The transfusion of 400 ml packed cells should increase hemoglobin by approximately 1.5 g/dL 4
• Consider switching to an alternative antiretroviral agent 1

Step 3: Resumption of Therapy

• If marrow recovery occurs following dose interruption, resumption of zidovudine may be appropriate using adjunctive measures such as erythropoietin 1
• Consider permanently switching to an alternative antiretroviral agent in patients with severe or recurrent anemia 1
• When using zidovudine with interferon/ribavirin for HCV co-infection, consider replacing zidovudine due to exacerbation of anemia 1

Special Considerations

• Patients co-infected with HIV/HCV receiving interferon and ribavirin should avoid zidovudine due to increased risk of anemia 1
• Drug interactions may exacerbate zidovudine-induced anemia:
  • Valproic acid can increase zidovudine levels by inhibiting glucuronidation 8
  • Ribavirin can exacerbate zidovudine-induced anemia 1
• For patients with renal impairment (CrCl <15 mL/min), dose adjustment to 100 mg every 6-8 hours is recommended 1
• In patients with pre-existing hematologic disorders like thalassemia, consider alternative antiretroviral agents 6

Common Pitfalls to Avoid

• Failing to check baseline hemoglobin before starting zidovudine 4
• Inadequate monitoring of blood counts during the first few months of therapy 1
• Continuing zidovudine despite significant anemia (Hgb <7.5 g/dL) 1
• Using erythropoietin in patients with very high endogenous erythropoietin levels (>500 IU/L), as they are unlikely to respond 7
• Overlooking drug interactions that may exacerbate anemia 8
• Failing to consider alternative antiretroviral agents in high-risk patients 1